Lipophilic complex

Cholanic acid also possesses the ability of transporting cations across a lipophilic membrane but the selectivity is not observed because it contains no recognition sites for specific cations. In the basic region, monensin forms a lipophilic complex with Na+, which is the counter ion of the carboxylate, by taking a pseudo-cyclic structure based on the effective coordination of the polyether moiety. The lipophilic complex taken up in the liquid membrane is transferred to the active region by diffusion. In the acidic region, the sodium cation is released by the neutralization reaction. The cycle is completed by the reverse transport of the free carboxylic ionophore. 

The brain uptake properties of 99m Tc-complexes with the MRP-20 ligand make it and its derivatives potential candidates for rCBF imaging applications. MRP-20 forms a neutral-lipophilic complex with the 99mTcO+3 core by loss of three ionizable protons from the ligand backbone (Fig. 3) [16]. "mTc-MRP-20 and several of its analogues show high brain uptake and retention and exhibit regional cerebral deposition patterns that are related to rCBF [16], This complex is in clinical trials in Europe. 

Figure 4. Schematic representation of the various processes involved in the transfer of metal ions from a complex medium to an organism. The free metal ion and the lipophilic complexes ML are effectively bioactive. Bioinactive complexes MY, present in the medium, can only contribute to biouptake processes via dissociation into M...

This hypothesis excludes lipophilic complexes [19,50] and complexes subject to accidental uptake via membrane permeases [51,52], for which the analysis would be basically different [5,18]. In this sense, we also disregard here any adsorption of M in the form of its complex ML. 

The lipophilic complex 99mTc(IV)-L,L-ECD (62) with a deprotonated L,L-ethylcysteine dimer as ligand, is clinically used as a cerebral perfusion imaging agent. It crosses the blood-brain barrier and... 

Starburst (TM) dendrimers with DTPA can contain 170 bound Gd(III) ions and have relaxivities (per bound Gd) up to 6 times that of Gd-DTPA (308). Both global and local motion contribute to the overall rotational correlation time. Attempts have been made to increase the re-laxivity of Gd(III) by optimizing the rotational correlation time via binding of Gd(III) to derivatized polysaccharides (309) and by binding lipophilic complexes to albumin in serum (310). The latter approach has achieved relaxivities as high as 44.2 mM l s1 for derivatized 72 (311). 

The only oral complex in clinical use is auranofin 92 (Ridaura), containing tetraacetyl-j8-D-thioglucose and triethyl phosphine ligands. Auranofin is a lipophilic complex, a monomer containing linear two-coordinate Au(I). 

Solvent extraction has become a common technique for the determination of formation constants, P , of aqneons hydrophilic metal complexes of type MX , particularly in the case when the metal is only available in trace concentrations, as the distribntion can easily be measnred with radioactive techniques (see also section 4.15). The method reqnires the formation of an extractable complex of the metal ion, which, in the simplest and most commonly used case, is an nn-charged lipophilic complex of type MA. The metal-organic complex MA serves as a probe for the concentration of metal ions in the aqueous phase through its equilibrium with the free section 4.8.2. This same principle is used in the design of metal selective electrodes (see Chapter 15). Extractants typically used for this purpose are P-diketones like acetylacetone (HAA) or thenoyltrifluoroacteone (TTA), and weak large organic acids like dinonyl naph-talene sulphonic acid (DNNA). 

The earliest and most widely studied particulate carriers for paramagnetic substances are the liposomes, either entrapping hydrophilic contrast agents within the internal aqueous phase, or incorporating lipophilic complexes in their phospholipidic bilayer membrane 100,101). 

The preparation of metal complexes from hydroxypyridinones is usually simple and straightforward—the more difficult task is generally the synthesis of the required ligand. There may also be difficulties in separating complex from ligand, especially for the more lipophilic complex S sublimation, used in the case of A -n-hexyl, may be more successful than recrystallization. 3-Hydroxy-4-pyridinones are for the most part accessible from hydroxypyranones. Reagents developed for analytical and separation purposes (preparative methods may be traced back... 

Results with Sr ] in Mice. While the results with Ag cryp-tate were encouraging, we sought further preliminary evidence of the potential value of labeled cryptates as blood-flow radiopharmaceuticals. There were several reasons for these studies the monovalent silver ion is very polarizable and thus may not be a general model for monovalent cations (5,17). In contrast, divalent cations form stronger inclusive cryptates than monovalent cations of the same ionic radii. On the other hand, the added charge of the divalent ion would require that the cryptand shield more charge if it is to result in an equally lipophilic complex. 

Wu S-Y, Robinson JR (1999) Transcellular lipophilic complex-enhanced intestinal absorption of human growth hormone. Pharm Res 16 1266-1272 Yamashita S, Saitoh H, Nakanishi K, Masada M, Nadai T, Kimura T (1987) Effects of diclofenac sodium and disodium ethylenediaminetetraacetate on electrical parameters of the mucosal membrane and their relation to the permeability enhancing effects in the rat jejunum. J Pharm Pharmacol 39 621-626... 

Fig. 21 Schematic representation of the procedure for preparing 188Re-labeled lipiodol. Mixing of the lipophilic complex [188Re(N)(diethyldithiocarbamato)2] with lipiodol causes the quantitative extraction and retention of the activity in the hydrophobic phase...

The orally active Au(I) complex auranofin (14) has a well-defined, linear two-coordinate structure (64). It is a lipophilic complex, but... 

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